Prostaglandin E₁ and nitroglycerin effects on canine epicardial conductance and distal coronary resistance vessels

Prostaglandin E₁ (PGE₁) has been reported to be a coronary vasodilator and has been considered clinically in the treatment of coronary vasospasm, but its mechanism of action is not known. To evaluate the vasomotor effect of PGE₁, epicardial coronary and distal resistance vessel responses were compared by PGE₁ and nitroglycerin infusion into the left anterior descending (LAD) artery of the closed-chest dog. Coronary angiography and ¹³³Xe washout flow measurements were used to quantitate proximal and distal vessel responses, respectively. To evaluate potential inhibitory actions, vessels were contracted by continuous LAD infusion of prostaglandin F(2α) (PGF(2α) or serotonin before dose-response testing with PGE₁ or nitroglycerin. PGE₁ alone produced a 20% dilation of the LAD in vivo but only with the highest dose (2.0 μg/min). PGE₁, however, did not reverse epicardial vessel constriction induced by PGF(2α) or serotonin. LAD flows (resistance vessel response) were increased comparably by PGE₁ alone and with PGF(2α) added (100 and 93% above control flow, respectively) but to a lesser extent with serotonin added (57% above control). In contrast, nitroglycerin completely reversed epicardial artery constrictions induced by PGF(2α) and serotonin. Our findings indicate that although PGE₁ is a vasodilator in vivo, it does not demonstrate a major effect in dilating epicardial conductance coronary arteries and therefore may not be beneficial in antagonizing endogenous contractile factors in treatment of coronary vasospasm. PGE₁ does increase coronary blood flow by dilating distal resistance vessels. The beneficial effects of PGE₁ in humans with unstable angina therefore are probably not due to vasorelaxing effects on epicardial coronary conductance arteries.